scholarly journals GoldVariants, a resource for sharing rare genetic variants detected in bleeding, thrombotic and platelet disorders: Communication from the ISTH SSC Subcommittee on Genomics in Thrombosis and Hemostasis

2021 ◽  
Author(s):  
Karyn Megy ◽  
Kate Downes ◽  
Marie‐Christine Morel‐Kopp ◽  
José M Bastida ◽  
Shannon Brooks ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Rare Genetic Variants ◽  
Platelet Disorders

scholarly journals Putative second hit rare genetic variants in families with seemingly GBA-associated Parkinson’s disease

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Muhammad Aslam ◽  
Nirosiya Kandasamy ◽  
Anwar Ullah ◽  
Nagarajan Paramasivam ◽  
Mehmet Ali Öztürk ◽  
...  
Keyword(s):  
Risk Factors ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Variants ◽  
Rare Variants ◽  
Alpha Synuclein ◽  
Younger Age ◽  
Targeted Treatments ◽  
Genes Encoding ◽  
Rare Genetic Variants

AbstractRare variants in the beta-glucocerebrosidase gene (GBA1) are common genetic risk factors for alpha synucleinopathy, which often manifests clinically as GBA-associated Parkinson’s disease (GBA-PD). Clinically, GBA-PD closely mimics idiopathic PD, but it may present at a younger age and often aggregates in families. Most carriers of GBA variants are, however, asymptomatic. Moreover, symptomatic PD patients without GBA variant have been reported in families with seemingly GBA-PD. These observations obscure the link between GBA variants and PD pathogenesis and point towards a role for unidentified additional genetic and/or environmental risk factors or second hits in GBA-PD. In this study, we explored whether rare genetic variants may be additional risk factors for PD in two families segregating the PD-associated GBA1 variants c.115+1G>A (ClinVar ID: 93445) and p.L444P (ClinVar ID: 4288). Our analysis identified rare genetic variants of the HSP70 co-chaperone DnaJ homolog subfamily B member 6 (DNAJB6) and lysosomal protein prosaposin (PSAP) as additional factors possibly influencing PD risk in the two families. In comparison to the wild-type proteins, variant DNAJB6 and PSAP proteins show altered functions in the context of cellular alpha-synuclein homeostasis when expressed in reporter cells. Furthermore, the segregation pattern of the rare variants in the genes encoding DNAJB6 and PSAP indicated a possible association with PD in the respective families. The occurrence of second hits or additional PD cosegregating rare variants has important implications for genetic counseling in PD families with GBA1 variant carriers and for the selection of PD patients for GBA targeted treatments.

Contribution of rare genetic variants to drug response in absence epilepsy

2021 ◽  
Vol 170 ◽  
pp. 106537
Author(s):  
Kenneth A. Myers ◽  
Mark F. Bennett ◽  
Bronwyn E. Grinton ◽  
Gabriel Dabscheck ◽  
Eunice K. Chan ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Drug Response ◽  
Absence Epilepsy ◽  
Rare Genetic Variants

scholarly journals A genome-first approach to aggregating rare genetic variants in LMNA for association with electronic health record phenotypes

2019 ◽  
Vol 22 (1) ◽  
pp. 102-111 ◽  
Author(s):  
Joseph Park ◽  
◽  
Michael G. Levin ◽  
Christopher M. Haggerty ◽  
Dustin N. Hartzel ◽  
...  
Keyword(s):  
Electronic Health Record ◽  
Genetic Variants ◽  
Health Record ◽  
A Genome ◽  
Rare Genetic Variants ◽  
Electronic Health

scholarly journals Identification of rare genetic variants in Juvenile Idiopathic Arthritis using whole exome sequencing

2015 ◽  
Vol 13 (S1) ◽  
Author(s):  
E Sanchez ◽  
S Grandemange ◽  
F Tran Mau-Them ◽  
P Louis-Plence ◽  
A Carbasse ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Whole Exome ◽  
Rare Genetic Variants

scholarly journals Rare Genetic Variants in Immune Genes and Neonatal Herpes Simplex Viral Infections

PEDIATRICS ◽  
2020 ◽  
Vol 147 (1) ◽  
pp. e20200687
Author(s):  
Lauren Cummings ◽  
Megan Tucker ◽  
Margaret Gibson ◽  
Angela Myers ◽  
Tomi Pastinen ◽  
...  
Keyword(s):  
Herpes Simplex ◽  
Genetic Variants ◽  
Viral Infections ◽  
Neonatal Herpes ◽  
Immune Genes ◽  
Rare Genetic Variants ◽  
Neonatal Herpes Simplex

scholarly journals Rare genetic variants prioritize molecular pathways for semaphorin interactions in Alzheimer’s disease patients

2021 ◽  
pp. 1-7
Author(s):  
Lubomir Balabanski ◽  
Dimitar Serbezov ◽  
Maya Atanasoska ◽  
Sena Karachanak-Yankova ◽  
Savina Hadjidekova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Variants ◽  
Molecular Pathways ◽  
Rare Genetic Variants

High-impact rare genetic variants in severe schizophrenia

2021 ◽  
Vol 118 (51) ◽  
pp. e2112560118
Author(s):  
Anthony W. Zoghbi ◽  
Ryan S. Dhindsa ◽  
Terry E. Goldberg ◽  
Aydan Mehralizade ◽  
Joshua E. Motelow ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Odds Ratio ◽  
High Impact ◽  
Psychiatric Genetics ◽  
Loss Of Function ◽  
Treatment Resistant ◽  
Complex Disorders ◽  
Extreme Phenotype ◽  
Case Selection ◽  
Rare Genetic Variants

Extreme phenotype sequencing has led to the identification of high-impact rare genetic variants for many complex disorders but has not been applied to studies of severe schizophrenia. We sequenced 112 individuals with severe, extremely treatment-resistant schizophrenia, 218 individuals with typical schizophrenia, and 4,929 controls. We compared the burden of rare, damaging missense and loss-of-function variants between severe, extremely treatment-resistant schizophrenia, typical schizophrenia, and controls across mutation intolerant genes. Individuals with severe, extremely treatment-resistant schizophrenia had a high burden of rare loss-of-function (odds ratio, 1.91; 95% CI, 1.39 to 2.63; P = 7.8 × 10−5) and damaging missense variants in intolerant genes (odds ratio, 2.90; 95% CI, 2.02 to 4.15; P = 3.2 × 10−9). A total of 48.2% of individuals with severe, extremely treatment-resistant schizophrenia carried at least one rare, damaging missense or loss-of-function variant in intolerant genes compared to 29.8% of typical schizophrenia individuals (odds ratio, 2.18; 95% CI, 1.33 to 3.60; P = 1.6 × 10−3) and 25.4% of controls (odds ratio, 2.74; 95% CI, 1.85 to 4.06; P = 2.9 × 10−7). Restricting to genes previously associated with schizophrenia risk strengthened the enrichment with 8.9% of individuals with severe, extremely treatment-resistant schizophrenia carrying a damaging missense or loss-of-function variant compared to 2.3% of typical schizophrenia (odds ratio, 5.48; 95% CI, 1.52 to 19.74; P = 0.02) and 1.6% of controls (odds ratio, 5.82; 95% CI, 3.00 to 11.28; P = 2.6 × 10−8). These results demonstrate the power of extreme phenotype case selection in psychiatric genetics and an approach to augment schizophrenia gene discovery efforts.

scholarly journals The genetics of interstitial lung diseases

2019 ◽  
Vol 28 (153) ◽  
pp. 190053 ◽  
Author(s):  
Raphael Borie ◽  
Pierre Le Guen ◽  
Mada Ghanem ◽  
Camille Taillé ◽  
Clairelyne Dupin ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Genetic Risk ◽  
Lung Diseases ◽  
Interstitial Lung Diseases ◽  
Systemic Diseases ◽  
Lung Volumes ◽  
Curative Therapy ◽  
Progressive Respiratory Failure ◽  
Rare Genetic Variants ◽  
Restrictive Physiology

Interstitial lung diseases (ILDs) are a set of heterogeneous lung diseases characterised by inflammation and, in some cases, fibrosis. These lung conditions lead to dyspnoea, cough, abnormalities in gas exchange, restrictive physiology (characterised by decreased lung volumes), hypoxaemia and, if progressive, respiratory failure. In some cases, ILDs can be caused by systemic diseases or environmental exposures. The ability to treat or cure these ILDs varies based on the subtype and in many cases lung transplantation remains the only curative therapy. There is a growing body of evidence that both common and rare genetic variants contribute to the development and clinical manifestation of many of the ILDs. Here, we review the current understanding of genetic risk and ILD.

ADDRESSING THE IMPACT OF RARE GENETIC VARIANTS IN EXTENDED/MULTIPLEX BIPOLAR FAMILIES

2019 ◽  
Vol 29 ◽  
pp. S837-S838
Author(s):  
Claudio Toma ◽  
Alexander D. Shaw ◽  
Richard J.N. Allcock ◽  
Anna Heath ◽  
Kerrie D. Pierce ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Rare Genetic Variants ◽  
The Impact
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